1. ICORD 2006 Kerstin Westermark Md, PhD, Assoc. prof. COMP Chairperson

2. ORPHAN DRUG CONTINUITY POLICY (From designation to MA and post-authorisation) EMEA presubmission COMP 69% SB COMP 5-yr review 10 yr. Market exclusivity access / profitability 50% uncertainty:very-high high less ODD COMP PA SAWP MA CHMP Orphan condition Therapeutic indication

3. The EU Orphan Legislation

4. EU Orphan Regulations l Regulation (EC) No 141/2000 of the European Parliament and of the Council on Orphan Medicinal Products of 16 December 1999 u For medicinal products for human use only u Not for medical devices u Not for food or food supplements u Not for medicinal products for veterinary use l Commission Regulation (EC) No 847/2000 of 27 April 2000

5. Committee for Orphan Medicinal Products (COMP) l COMP u 31 members (3 patient representatives) + Chairman u Tasks – Opinions on designation – Advising on general EU policies – International co-operation

6. Criteria for Orphan Designation Prevalence (< 5 / 10,000) Insufficient return on investment (costs > expected revenues) Life-threatening or chronically debilitating Life-threatening, seriously debilitating or serious and chronic Available “methods” for diagnosis / prevention / treatment NO YES Significant benefit / non satisfactory “Prevalence” criterion“Seriousness” criterion “Sign. benefit” criterion

7. Incentives for Designated Products Main EU Incentives l Ten years exclusivity from the date of marketing authorisation l Protocol assistance from the EMEA l Direct access to Centralised Procedure l Fees reduction for centralised applications l Priority access to EU research programs National Incentives l Inventory published on Commission Web-site

8. Orphan Designation

9. Major Milestones 2001200020052003 Regulation 141/2000 adopted Dec1999 20022004 Regulation 847/2000 adopted 1 st Meeting of COMP 1 st Application for Orphan Designation received on 28 April Apr 00 Aug 00 1 st Orphan Medicinal Products Designated Aug 01 1st Orphan Medicinal Products Authorised 2006 Oct 06 401 OMP Designated and 30 OMP Authorised

10. COMP MEETING Intent to file letter Application submission ValidationEvaluation List of questions / oral explanation Opinion Procedure for Designation DAY 60DAY 1DAY 90 Decision

11. Status of Orphan Applications 2000200120022003200420052006Total No. of applications submitted 7283808710811886634 Positive COMP Opinions26644354758872422 Commission Decisions14644955728859401 Final Negative COMP Opinions 013140211 Withdrawals6273041223015171 Up to 17 October 2006

12. Status of Orphan Applications Up to 17 October 2006

13. Protocol Assistance for OMP

14. Protocol Assistance Protocol Assistance (PA) = Scientific Advice (SA) ( Article 6 of Regulation (EC) No 141/2000) Sponsor can ask questions on Quality aspects Preclinical development Clinical development Significant benefit Regulatory aspects

15. New regulation of European Parliament and Council Regulation (EC) 726/2004 - Main key aspects for SA Scientific Advice Working Party Modernised structures allowing the development of advice for companies, in particular, small and medium sized enterprises More general and in-depth SA SA for the development of new therapies Contacts with in particular patient organisations and health- care professionals' associations NEW FRAMEWORK FOR SA & PA Legal requirements

16. NEW FRAMEWORK FOR SA & PA Procedure A streamlined 70-day procedure with possible finalisation in 40 days Planning phase with: Earlier appointment of coordinators/experts Presubmission meeting (optional) to: Receive early feedback Increase quality of request before start of procedure Recommended for first time users of SA, for Protocol assistance, for SMEs, for SA on “specific types of medicinal products and therapies”, and “broad and more general advice”.

17. Summary of New Framework for SA / PA l Extended scope to provide also broader and more general advice l New faster procedure with involvement of experts already in the pre-submission phase l Broad definition of follow-up l Increased transparency and communication

18. Scientific Advice / Protocol Assistance Procedures (Sept 06)

19. Guidance Documents l Guideline on format and content of applications for designation as orphan medicinal products and on the transfer of designations from one sponsor to another /ENTR/6283/00 l EMEA guidance for companies requesting scientific advice (SA) and protocol assistance (PA) EMEA-H-4260-01-Rev.3

20. Guidance Documents (cont) l Points to consider on the calculation and reporting of the prevalence of a condition for orphan designation EMEA/COMP/436/01 l Guideline on the elements required to support the medical plausibility and the assumption of significant benefit for an orphan designation (EMEA/COMP/66972/2004) l Guideline on clinical trials in small populations CHMP/EWP/83561/2005

21. Orphan Drug Achievements in the EU – Information l COMP report to the Commission in relation to Article 10 of Orphan Regulation 141/2000 on Orphan Products EMEA/35218/2005 Final l General report on the experience acquired with the application of Regulation (EC) No 141/2000 on orphan medicinal products during the first five years of publication http://ec.europa.eu/enterprise/pharmaceuticals/orphanmp/doc/orphan_en_ 06-2006.pdf l 7/9/06: Inventory of Community and Member States' incentive measures to aid research, marketing, development and availability of orphan medicinal products. Revision 5 http://ec.europa.eu/enterprise/pharmaceuticals/orphanmp/doc/inventory_2 006_08.pdf